Desipramine induces cardiac beta-adrenergic sensitivity decrease in major depressed patients without relationship to therapeutic response.

Nineteen major depressed inpatients were treated over three weeks with desipramine. Cardiac beta-adrenergic receptor sensitivity was evaluated by an isoproterenol test before and after the three-week treatment. Desipramine induced a beta-adrenergic sensitivity decrease in most of the patients: I 20 (isoproterenol dose necessary to increase by 20 beats/min.

[Amineptin dependence. Detection of patients at risk. Report of 8 cases].

The authors relate eight cases of amineptine dependency collected between 1980 and 1988 in 7 women and 1 man treated in the CHU of Besançon (France). The pharmacodependency appeared to be limited mainly to an abuse and a psychic dependence, i.e.

[Compliance, subdosage and overdosage of antidepressive agents in the first prescription in a hospital milieu].

It is common clinical experience that depressed patients comply poorly with their treatment schedules. In a retrospective study, the authors studied the compliance with the tricyclic antidepressant treatment (TCA) in 1,023 in-patients and evaluated the frequency of the plasma levels under or above the therapeutic range, following a first prescription of TCA. To describe the adherence to the TCA regimen, the investigators have classified patients as either "compliant" or "bad compliant" on the basis of two different arbitrary dividing points: plasma levels of tertiary OR secondary amine lower than 20 ng/ml, or plasma levels of tertiary AND secondary amine lower than 20 ng/ml.

[Valpromide-amitriptyline interaction. Increase in the bioavailability of amitriptyline and nortriptyline caused by valpromide].

Valpromide is largely used in the therapy of affective disorders for its presumed thymoregulating activity. So, it is often associated with tricyclic antidepressant treatment. Previous clinical studies lead us to consider the possibility of an interaction between valpromide and tricyclic antidepressants, interaction which could result in an increase of antidepressant plasma concentrations.

Desipramine dose prediction based on 24-hour single-dose levels: feasibility and validity.

The authors present a prospective study of a rapid desipramine dose adjustment on the basis of a 24-hour plasma concentration after a single 150 mg dose. For this, they use a prediction table constructed from data in the literature showing strong correlation between steady-state plasma levels and 24-hour single-dose levels. Despite the fact that desipramine action is not always linear, the method appears to be feasible and valid.

Amitriptyline: linear or nonlinear kinetics in every day practice?

The linearity of the (AMT) kinetics of amitriptyline has been tested in 135 depressed dosed twice daily by measuring plasma. Their (AMT) and nortriptyline (NT) levels under steady-state conditions. The AMT concentration/dose ratios at low and high dosages were not significantly different and there was a linear relationship between the dose ratios and the concentration ratios.

Cardiac beta-adrenergic sensitivity in depression: relation with endogenous subtype and desipramine response.

The authors studied the responsiveness of cardiac beta-receptors to isoproterenol, a noradrenergic agonist, in 29 depressed patients and 13 control subjects. They showed a significantly lower sensitivity in depressed patients as compared with the control subjects. Focussing on the group of depressed patients without antidepressant treatment in the month preceding the study (n = 15) in order to avoid a bias, the following significant results were obtained: cardiac beta-adrenergic receptor sensitivity was lower in patients suffering from endogenous depression than in those suffering from reactive depression (as classified by Newcastle Scale).

Valpromide increases the plasma concentrations of amitriptyline and its metabolite nortriptyline in depressive patients.

The effects of valpromide on amitriptyline (AMT) and nortriptyline (NT) plasma levels were examined in 20 depressed inpatients. They all were treated with AMT, 125 mg once daily, and 10 patients also received 600 mg of valpromide daily after 10 days on AMT. In the 10 patients receiving valpromide in addition to AMT, the mean AMT level increased from 70.

Biotransformation of amitriptyline in man: interaction with phenothiazines.

The biotransformation modification of amitriptyline by phenothiazines has been studied in 65 depressive inpatients. Thirty-four of them were treated with oral amitriptyline and 31 with a combination of amitriptyline and phenothiazine. Urinary and plasmatic results showed a decrease in hydroxylated metabolites of amitriptyline (OHAMTc and OHAMT) in patients with added phenothiazine.

Biological markers in depression. Monoamine metabolites in urine of depressed patients and normal subjects.

Urinary elimination of HVA, MHPG and 5-HIAA was studied in 22 depressed inpatients before and after 28 days of antidepressant treatment. Mean values did not change significantly during treatment, and were not related significantly to recovery in patients. Some marked changes in urinary metabolite levels were, however, observed in individual patients, and could be related to changes in their depression.

[Dexamethasone test: suppressors and non-suppressors, what's the difference?].

In sixty-six depressed in-patients, 20 of them showed marked resistance to suppression after dexamethasone. The authors found no difference between the two subgroups of suppressors and non suppressors, when considering the following parameters: age, sex, duration of illness, number of prior episodes, family history, intensity of depression, response to antidepressant treatment, relapses, diagnoses. Furthermore the normalization of DST after a 28 day treatment did not systematically correlate with a good clinical improvement.

Biotransformation of amitriptyline in alcoholic depressive patients.

The biotransformation of amitriptyline (AMT) during steady state conditions was studied in plasma and urine from 11 nonalcoholic and 10 alcoholic depressive inpatients treated with oral AMT. The 2 groups of patients had a different pattern of biotransformation. The Demethylation of AMT was lower in alcoholic than in nonalcoholic depressive patients, and conjugation and hydroxylation of AMT were also more marked in the former group.

Biotransformation of amitriptyline in depressive patients: urinary excretion of seven metabolites.

The urinary excretion of amitriptyline (AMT) and seven of its metabolites was studied by mass spectrometry in 10 depressive in-patients treated to steady-state condition with oral amitriptyline. An average of 68.3% of the dose was recovered in the urine, of which 68.

Relationship between the plasma concentration of clomipramine and desmethylclomipramine in depressive patients and the clinical response.

Thirty one in-patients suffering from depression were treated orally with clomipramine (C1) at various dosage, for 28 days, after a "wash-out" period of three days. In 17 patients receiving 75 mg per day of C1, steady state plasma levels of C1 were reached at Day 14, and steady state plasma levels of its active metabolite, desmethylclomipramine (DMC1), were reached at Day 21. In contrast, in 7 other patients receiving a dosage increasing to 150 mg per day at Day 7, mean plasma levels of C1 and DMC1 continued to rise during the entire treatment period.

Clinical pharmacology of viloxazine hydrochloride.

Plasma concentrations of viloxazine were determined in twenty depressed inpatients during 4 weeks of treatment with progressively increasing dosage. Viloxazine plasma levels varied markedly during the day, due to the short half-life of the drug. Plasma levels rose to peak values after 7-10 days of treatment and then decreased, perhaps due to enzymatic induction by viloxazine.

[Clomipramine and desmethylclomipramine: relationship between plasma levels and clinical effect (author's transl)].

Pharmacokinetic can perhaps explain that about 30% of depressed patients do not respond to tricyclic antidepressants. Studies of the relationship between the pharmacokinetic and pharmacological effects of the tricyclic antidepressants are particularly important. Clomipramine is a tricyclic antidepressant widely used.

Effect of selective midbrain and diencephalic 5,7-dihydroxytryptamine lesions on serotonin content in individual preopticohypothalamic nuclei and on serum luteinizing hormone level.

Injection of the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the midbrain dorsal (DR) or median (MR) raphe nucleus of castrated and normal male rats was followed by measurement of serum luteinizing hormone (LH) level and the 5-hydroxytryptamine (5-HT) content of several hypothalamic and amygdaloid nuclei. Only the DR lesions lead to a significant decrease (42%) in serum LH level in normal rats. The elevated LH level in castrated animals was not affected by either lesion.